Biodegradable polymers are useful in many medical applications, especially drug delivery devices. Many of the biodegradable polymers used are of the thermoplastic type. Polymers made of thermoplastic resins typically liquify or soften at elevated temperatures and resolidify upon cooling. This type of polymer is generally formed into the desired structure for use as sutures, surgical clips, staples, implants and the like, prior to insertion into the body. Once inserted into the body, these polymers retain their shape.
For drug delivery devices, the drug is generally incorporated into the polymeric composition and formed into the desired shape outside the body. This solid implant is then typically inserted into the body of a human, animal, bird or the like through an incision. Alternatively, small discrete particles composed of these polymers can be injected into the body by a syringe. Preferably, however, certain of these polymers can be injected via syringe as a flowable polymeric composition.
Flowable polymeric compositions for use as biodegradable controlled release drug delivery systems are described in the patent literature, e.g., U.S. Pat. Nos. 4,938,763; 5,077,049; 5,324,519; 5,632,727; 5,599,552; 5,702,716; 5,487,897; 5,660,849; 5,278,201; 5,198,220; 5,447,725; 5,242,910; 5,733,950; 5,739,176; 5,945,115; 5,744,153; 5,759,563; 5,660,849; and 6,143,314.
These compositions are administered to the body in a flowable physical state, typically via syringe. Once in the body the composition transforms into a solid. One type of polymeric composition consists of a nonreactive thermoplastic polymer or copolymer dissolved or dispersed in an organic solvent. This polymeric solution is placed into the body where the polymer gels or precipitatively solidifies upon the dissipation or diffusion of the solvent into the surrounding body tissues. Also, improved polymeric compositions that form a solid matrix in situ thereby forming an implant for sustained release of a medicament over a desired period of time are described in the patent literature.
An example of a commercially available product that utilizes this technology is the ATRIDOX™ product which is a subgingival controlled-release product composed of a two syringe mixing system. Syringe A contains 450 mg of the ATRIGEL® Delivery System, which is a bioabsorbable, flowable polymeric formulation composed of 36.7% poly(DL-lactide)(PLA) dissolved in 63.3% N-methyl-2-pyrrolidone (NMP). Syringe B contains the antibiotic doxycycline hyclate which is equivalent to 42.5 mg doxycycline.
K. P. Andriano et al., J. Biomed. Mater. Res. (Appl. Biomater.), 53: 36-43 (2000), disclose preliminary in vivo studies on the osteogenic potential of bone morphogenetic proteins delivered from an absorbable puttylike polymer matrix. R. L. Dunn et al., Portland Bone Symposium 1999, Oregon Health Sciences University, pages 522 to 528, studied the osteoinductivity of bone morphogenetic proteins delivered from an absorbable putty-like matrix.
The optimal control of release rate of certain bone growth promoting compounds, especially certain small molecule, is a never-ending quest for sustained release implants including but not limited to the flowable compositions. Consequently, there is the need for a flowable composition in which the rate of delivery of certain bone growth promoting compounds can be more readily controlled, especially for a compound which requires sustained release over a longer time period.